The Hox proteins are key transcription factors that regulate anterior-posterior patterning of all animal embryos. Few bona fide targets are known for these important development regulators and only a single cofactor, extradenticle, has been identified. Hox proteins function both as transcriptional activators and transcriptional repressors and the modes of regulating Hox activity are poorly understood. The goal of this research is the identification of genetic cofactors that can modulate Hox activity. Overlapping genetic roles and pleiotropic mutant phenotypes have hampered traditional forward mutagenetic approaches designed to identify proteins that functionally interact with Hox transcription factors. This proposal is designed to identify genes that cooperatively function with the Hox gone AbdominaI-B (Abd-B). Misexpression of Abd-B and a library of target genes will identify positive genetic interactors that will then be investigated to further our understanding of the ways in which this fundamentally important family of transcription factors regulates embryonic development. This work will lead to a more detailed knowledge of how Hox proteins achieve target gene specificity and function as both positive and negative transcriptional regulators.